Optimal Control for Simple Linear Hybrid Systems

This paper studies optimal time-bounded control in a simple subclass of linear hybrid systems, which consists of one continuous variable and global constraints. Each state has a continuous cost attached to it, which is linear in the sojourn time, while a discrete cost is attached to each transition taken. We show the corresponding decision problem to be NP-complete and develop an FPTAS for finding an approximate solution. We have implemented a small prototype to compare the performance of these approximate and precise algorithms for this problem. Our results indicate that the proposed approximation schemes scale. Furthermore, we show that the same problem with infinite time horizon is in LOGSPACE.</p

Pediatric ophthalmic indications for examination under anesthesia in Ilorin, Nigeria

Objective: To determine the ophthalmic indications and challenges for pediatric ocular examination under anesthesia (EUA).Methods: The surgical register and patients’ records of children who underwent EUA between 1990 and 2007 were examined to document patients’ bio data, diagnoses and details of procedures and anesthesia.Results: Thirty-nine children underwent EUA during the 18-year period. The indications included congenital glaucoma (20 cases, 21.3%) and congenital cataract (5 cases, 12.8%). There were two cases each (5.1%) of microphthalmia, megalocornea, and squint. A case each of other indications constituted the remaining 10.3%.Conclusion: The commonest ophthalmic indication for EUA among children is congenital glaucoma. Most of the children (36, 92.3%) had inhalational anesthesia administered by anesthetists at great cost to their parents. Werecommend the use of ketamine anesthesia administered by nonanesthetist with some training in anesthetic resuscitation procedure, for short pediatric procedure such as EUA in resource-challenged settings

Effect of Variety, Seed Rate and Row Spacing on the Growth and Yield of Rice in Bauchi, Nigeria

Field experiments were conducted at Abubakar Tafawa Balewa University, Fadama Farm Bauchi, during the rainy seasons of 2006 and 2007 to study the effects of variety, seeding rate and row spacing on growth and yield of rice. Two varieties of rice; Ex – China (Indigenous and upland/lowland) and NERICA-1 (improved and upland), three seeding rates (32, 54 and 75 kg/ha) and four row spacings (15, 20, 25 and broadcast) were used during the study. The treatments were combined and laid in a split – split plot design with three replications. Variety was placed in the main plot, seeding rate in the sub plot while row spacing was placed in sub –sub plot. Data were collected on parameters such as plant height, number of tillers per plant, spikes per hill, spikelets per spike and number of seeds per spike, seed weight per hill, 1000 grain weight and yield kg ha-1 and analyzed using analysis of variance procedure for split – split plot and significant differences among the treatment means were separated using the Duncan multiple range test (DMRT). Variety Ex-China produced significantly (P&lt;0.05) higher numbers of tillers per plant and spikes per hill. However, NERICA-1 produced significantly (P&lt;0.05) higher numbers of spikelets per spike, seeds per spike, weight of seed per spike, weight of seed per hill, 1000 grain weight and yield in kg ha-1 than Ex-China. Row spacings of 15, 20 and 25cm also had significant effects on the number of tillers per plant, number of spikes per hill, number of spikelets per spike, number of seeds per spike, weight of seed per spike, weight of seed per hill, 1000 grain weight and yield kg ha-1 over the control. From the factors studied, seeding rate did not show any significant difference during the two years of investigation. Interactions were also observed among the factors studied. Therefore, row spacings irrespective of the method used, or hole planting of rice could be more appropriate for optimum grain yield.Key words: Seed rate, Row spacing, Spike

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Modulation of Aryl Hydrocarbon Receptor (AHR)-Regulated Metabolic Enzymes by Arsenic Trioxide and its Thioarsenical Metabolite

Arsenic trioxide (ATOIII) has evolved into a successful therapy for acute promyelocytic leukemia (APL), however, being an arsenical, it retains at its core the hypertoxic characteristics of that notorious metalloid. Such inherent toxicity causes a constellation of complications in APL patients, including hepatotoxicity, and may also limit expanding clinical ATOIII applications. In humans, ATOIII undergoes progressive metabolism into diverse methylated intermediates/products, which can, at least partly, be responsible for the overall toxic outcome of ATOIII. The thio-methylated MMMTAV is one of these metabolites that have been identified in ATOIII-treated APL patients. Arsenicals are well-known modulators of cytochrome P450 (CYP) enzymes, most notably the aryl hydrocarbon receptor (AHR)-regulated CYP1A1/1A2. These enzymes are pivotal for metabolism of endobiotics and commercial drugs, therefore, modifying their activity can entail a disease state or clinical drug-drug interactions, respectively. Additionally, altering CYP1A1/1A2 can aggravate environmental toxicants impact through their activation or diminished elimination. Therefore, this work aimed to determine the possible effects of ATOIII and MMMTAV on constitutive and TCDD-inducible levels of hepatic CYP1A1/1A2 using in vivo and in vitro models. We also aimed to investigate in vivo effects of ATOIII on hepatic non-AHR-regulated CYP enzymes with the associated perturbations in arachidonic acid (AA) metabolism. Finally, we explored in vivo effects of ATOIII on drug transporters. For this purpose, C57BL/6 mice were intraperitoneally injected with 8 mg/kg ATOIII (or 12.5 mg/kg MMMTAV) with or without 15 μg/kg TCDD for 6 and 24 h. Furthermore, HepG2 and Hepa1c1c7 cell lines were treated with varying concentrations of ATOIII (or MMMTAV) with or without 1 nM TCDD for 6 and 24 h. In C57BL/6 mice, ATOIII inhibited TCDD-mediated induction of hepatic CYP1A1/1A2 mRNA, proteins, and activities. Significant reductions in CYP1A2, but not CYP1A1, protein and activity were observed at basal levels. In HepG2 cells, a similar inhibitory effect was observed in inducible CYP1A1/1A2 at all expression levels. Such inhibition was transcriptionally regulated by interfering with AHR-mediated activation of the xenobiotic response element (XRE). Also, post-translational modification through up-regulated heme oxygenase 1 (HMOX1) might be, at least partially, implicated in reducing enzyme activity. In Hepa1c1c7 cells, TCDD-inducible CYP1A1/1A2 expressions were increased at all expression levels, while only basal levels of mRNA transcripts, in addition to protein in case of CYP1A2, were up-regulated. Such contradiction with the in vivo murine model was attributed to transcriptional regulation related to AHR nuclear accumulation as well as XRE activation. Moreover, post-transcriptional and post-translational mechanisms caused increased production and decreased degradation of CYP gene products. MMMTAV ultimately increased CYP1A1/1A2 inducible activities in C57BL/6 mice. The same pattern of effect was also observed in Hepa1c1c7 cells. At early stage of CYP1A1 gene expression, i.e., mRNA transcripts formation, a significant decrease was obtained in both models. Such effect was only explained by transcriptional regulation mediated by interference with AHR-mediated XRE activation. As opposed to these murine models, the effect on inducible CYP1A1 in HepG2 cells was consistently inhibitory across all expression levels. Similarly, this inhibition was attributed to transcriptional regulation at the level of XRE activation. We also showed that in vivo alteration of CYP enzymes by ATOIII goes beyond AHR-regulated CYP1A subfamily to include other CYP families (CYP2, CYP3, and CYP4). ATOIII altered hepatic AA metabolism in C57BL/6 mice through modulating the underlying network of enzymes. Such modulation impacts AA biotransformation pathway from its beginning at the step of AA liberation and extends through the eicosanoids (e.g., hydroxyeicosatetraenoic acids (HETEs))-generating cyclooxygenases, lipoxygenases, and CYP enzymes routes. ATOIII suppressed Cyp2e1, while induced Cyp2j9 and most of Cyp4a and Cyp4f, causing 17(S)-HETE and 18(R)-HETE increase, and 18(S)-HETE decrease. ATOIII also induced Cyp4a10, Cyp4a14, Cyp4f13, Cyp4f16, and Cyp4f18, causing 20-HETE elevation. In conclusion, modulating CYP1A enzymes by ATOIII and MMMTAV implies their possible involvement in clearance-related consequences for the substrates of these enzymes such as interactions with co-administered drugs, like granisetron which is widely used anti-emetic for chemotherapy-induced nausea and vomiting, or suboptimal environmental toxicants elimination. Also, Modifying the homeostatic production of bioactive AA metabolites can entail toxic events that compromise overall body tolerability to ATOIII treatment. Additionally, this situation may be aggravated by unfavorable changes in the expression of ATOIII transport systems, such as increased expression of influx aquaporin channels, with ensuing enhancement of its toxicity

HLA-DRB1 alleles in children with post-streptococcal acute glomerulonephritis

To investigate the association between HLA-DRB1 alleles and post-streptococcal acuteglomerulonephritis (PSAGN), 32 children withPSAGN and 380 healthy subjects from the samelocality were typed for DRB1alleles usingpolymerase chain-reverse hybridization technique.Patients with PSAGN have significantly increasedfrequency of both DRB1* 03011 (46.9 vs. 19.2% incontrols, P = 0.00025) and DRB1* 1105 (31.1 vs.15.6% in controls, P = 0.0097). However, aftercorrection of P values, only the difference for DRB1*03011 remains significant (P = 0.025). Their relativerisks are significantly high [3.71, confidence interval(Cl) = 1.8-7.8, and 3.57, Cl = 1.4-8.9 respectively].No significant differences in the frequency of bothalleles arc observed among patients with differentgrades of hypertension, proteinuria or hematuria.Conclusions: DRB1* 03011, and presumably 1105,alleles confer susceptibility to PSAGN. However theseverity of the disease is not determined by these twoalleles

Predictors of Medication Adherence and Blood Pressure Control among Saudi Hypertensive Patients Attending Primary Care Clinics: A Cross-Sectional Study

Purpose To assess the level of medication adherence and to investigate predictors of medication adherence and blood pressure control among hypertensive patients attending primary healthcare clinics in Makkah, Saudi Arabia. Patients and methods Hypertensive patients meeting the eligibility criteria were recruited from eight primary care clinics between January and May 2016 for this study. The patients completed Arabic version of Morisky Medication Adherence Scale (MMAS-8), an eight-item validated, self-reported measure to assess medication adherence. A structured data collection form was used to record patients’ sociodemographic, medical and medication data. Results Two hundred and four patients, of which 71.6% were females, participated in the study. Patients’ mean age was 59.1 (SD 12.2). The mean number of medication used by patients was 4.4 (SD 1.89). More than half (110; 54%) of the patients were non-adherent to their medications (MMAS score 65 years (OR 2.0 [95% CI: 1.0–4.2; P = 0.04]), and being diabetic (OR 0.25 [95% CI: 0.1–0.6; P = 0.04]) were found to be independent predictors of medication adherence. Conclusion Medication adherence is alarmingly low among hypertensive patients attending primary care clinics in Saudi Arabia which may partly explain observed poor blood pressure control. There is a clear need to educate patients about the importance of medication adherence and its impact on improving clinical outcomes. Future research should identify barriers to medication adherence among Saudi hypertensive patients

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Laser and radiofrequency-induced hyperthermia treatment via gold-coated magnetic nanocomposites

Alsayed AM Elsherbini1, Mahmoud Saber2, Mohamed Aggag2, Ahmed El-Shahawy2, Hesham AA Shokier11National Institute of Laser Enhanced Science, 2Children&amp;#39;s Cancer Hospital, Cairo, EgyptIntroduction: The current radiofrequency ablation technique requires invasive needle placement. On the other hand, most of the common photothermal therapeutic methods are limited by lack of accuracy of targeting. Gold and magnetic nanoparticles offer the potential to heat tumor tissue selectively at the cellular level by noninvasive interaction with laser and radiofrequency.Methods: Gold nanospheres and gold-coated magnetic nanocomposites were used for inducing hyperthermia to treat subcutaneous Ehrlich carcinoma implanted in female mice.Results: In mice treated with gold nanospheres, tumors continued to grow but at a slow rate. In contrast, more than 50% of the tumors treated with gold-coated magnetic nanocomposites completely disappeared.Conclusion: This simple and noninvasive method shows great promise as a technique for selective magnetic photothermal treatment.Keywords: laser, hyperthermia, gold magnetic nanocomposites, Ehrlich carcinom